Fiber-Based Hydrogels for Designing Viscoelastic Responses in Particle-Based Biomaterials That Support Embedded 3D Printing.

Viscoelastic biomaterials that exhibit biomimetic responses to applied stresses are important in studying physiology and designing biomaterial scaffolds. Particle-based hydrogels offer potential for engineering viscoelasticity through the design of both the component microparticles and their processing into bulk particle-based materials. When particles are not cross-linked to one another, particle movements in response to strain can potentially relieve applied stresses and facilitate the material's use in dynamic processes like bioprinting. In particle-based hydrogels based on spherical hydrogel microparticles (HMPs), particle movement is restricted by contact with immediately adjacent HMPs. In comparison, fiber-based hydrogel systems leverage high-aspect-ratio microfiber components with long-range interactions. Here, microfibers with aspect ratios of ∼15:1 length/diameter are used to form particle-based hydrogels to compare how interparticle interactions at increased length scales alter properties compared to particle-based hydrogels based on spherical HMPs. Like particle-based hydrogels formed from spherical HMPs, those formed from fiber HMPs exhibit viscoelasticity with shear-thinning and self-healing behaviors. But fiber-based materials allow enhanced control over bulk stress relaxation times (T1/2 ∼ 1-100+ s) across a range of applied strains (σ ∼ 2.5%-50%) in a packing density-dependent fashion. Fiber-based systems relaxed stresses continuously and to a greater degree at low strains in comparison to HMP systems. Dynamic interfiber interactions in fiber-based hydrogels also supported embedded printing, where perfusable channels can be printed into fiber-based hydrogels stabilized by physical interfiber interactions. Taken together, fiber-based hydrogels offer opportunities for designing complex biomaterial scaffolds, including allowing control over viscoelastic properties through hydrogel design and control over heterogeneous 3D structures through embedded printing.